biostudies-literatureMorales-Rosado JANational Heart, Lung, and Blood InstituteNHLBI NIH HHS549-559https://www.ebi.ac.uk/biostudies/studies/S-EPMC7779664biostudies-literatureUnknown35(3)<h4>Purpose</h4>Describe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic variation detected by next-generation sequencing (NGS) with comprehensive annotation and functional studies.<h4>Methods</h4>Seventy ST cases on clopidogrel identified from the PLATO trial (n = 58) and Mayo Clinic biorepository (n = 12) were matched 1:1 with controls for age, race, sex, diabetes mellitus, presentation, and stent type. NGS was performed to cover the entire CYP2C19 gene. Assessment of exonic variants involved measuring in vitro protein expression levels. Intronic variants were evaluated for potential splicing motif variations.<h4>Results</h4>Poor metabCardiovascular drugs and therapyNext-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics.PMC7779664U01 HL128606Pereira NLJenkins GDBaheti SRoger VLWeinshilboum RStorey RFGoel KJohnson SZhang LKlee EWWang LMorales-Rosado JAGoodman SGEckloff BWJames SBielinski SJWallentin LBlack JLRihal CSSicotte HEriksson NAkerblom AfalseNext-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics.<h4>Purpose</h4>Describe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic variation detected by next-generation sequencing (NGS) with comprehensive annotation and functional studies.<h4>Methods</h4>Seventy ST cases on clopidogrel identified from the PLATO trial (n = 58) and Mayo Clinic biorepository (n = 12) were matched 1:1 with controls for age, race, sex, diabetes mellitus, presentation, and stent type. NGS was performed to cover the entire CYP2C19 gene. Assessment of exonic variants involved measuring in vitro protein expression levels. Intronic variants were evaluated for potential splicing motif variations.<h4>Results</h4>Poor metab2021-01-01T00:00:00Z2021 Jun2026-05-09T04:18:10.906Z2025-04-04T22:03:58.213ZS-EPMC77796643262359810.1007/s10557-020-06988-w